We propose to study virus glycoproteins and their interaction with specific antibody to understand the molecular mechanism of neutralization. Hybridoma cells will be used to obtain specific antibody for different antigenic determinants on the La Crosse GI glycoprotein. La Crosse virus has been selected because it exhibits unique properties. Trypsinization of La Crosse results in a slight loss in infectivity and cleavage of the GI glycoprotein (120,000 daltons) to two different size polypeptides (67,000 and 95,000 daltons). This trypsinized virus is neutralized one log or less by specific antibody under conditions where normal virus is neutralized greater than four logs. Antibody binds to the polypeptides remaining in the envelope after trypsinization, resulting in a large population of infectious virus-antibody complexes. This indicates antibody can bind to various antigenic determinants on G1, but only antibody binding at a critical site leads to neutralization. The portion of G1 which is cleaved off by trypsin appears to contain this critical site. The infectivity of trypsinized virus indicates that either the antibody binding site is not the same as the cell receptor binding site or there is more than one site available for attachment to cells. These unusual properties provide a means to look at a single species of glycoprotein molecules to determine which site(s) must be present for infectivity, which sites can bind with antibody, and which site(s) when bound with antibody results in noninfectious virus.